We have under observation a group of individuals with documented poststreptococcal glomerulonephritis (PSGN), who have been under our follow-up for periods up to 18 years. The majority have evidence, clinically and morphically, of irreversible renal disease. Utilizing this unique clinical material, our project has the following objectives: 1. To explore the role of cellular immunity in the pathogenesis of chronicity in PSGN by examining the thesis that lymphocyte tolerance to altered glomerular basement membrane antigens permits the mounting of a humoral immune mechanism directed against the glomerulus. 2. To examine the role of intra-renal vascular disease, a non-immune mechanism, for progression in PSGN which could cause glomerular sclerosis on an ischemic basis, by an analysis of the relationships among hypertension, fibrohyaline intimal disease of renal arterioles and glomerular sclerosis in PSGN as compared to essential hypertension. Similar observations will be made in experimental forms of rat hypertension and glomerulonephritis, alone and in combination, to supplement the morphologic and physiologic studies in man.